The regulation of transcription and expression of C-type virus-specific RNA will be studied in exogenously infected and uninfected mouse cells. Virus-specific sequences will be identified by hybridization of extracted RNA with complementary DNA (cDNA) probes prepared from the viruses by the endogenous reverse transcriptase reaction. Mouse cells exogenously infected with Moloney murine leukemia virus will be studied: (1) Pulse-labeled virus-specific RNA will be identified and studied using an excess cDNA hybridization system. (2) Virus-specific proteins will be identified by immuno-precipitation with monospecific antisera. (3) Intracellular virion precursor particles will be identified and characterized. The expression of endogenous C-type virus-specific RNA in cells derived from inbred BALB/c mice will be studied. Monospecific cDNA probes which can recognize each of the BALB/c endogenous viruses individually will be prepared. Using the monospecific cDNA probes, the following cells will be studied: (a) uninfected BALB/c 3T3 cells, (b) BALB/c 3T3 infected or transformed with DNA tumor viruses and their temperature sensitive mutants, and (c) cells transformed by chemical carcinogens, and other means. We hope these studies will indicate if endogenous C-type viruses expression is linked to malignant cell transformation. The location of endogenous virus-specific sequences in fractionated chromatin will be studied. Cell lines will be developed which contain only one or a small number of endogenous virus DNA copies, in differing states of expression. The location of the virus-specific DNA sequences in template active and inactive chromatin will be studied using cDNA probes. These studies may indicate if endogenous C-type virus expression is controlled at the level of chromatin structure and function.